1st Paediatric Emergency ConferenceKuwait October 2011

Sickle Cell Disease – Optimising Paediatric

Emergency Care

Dr. D. A Jarvis

Disclaimer

I have no actual or potential conflict of interest to declare.

Photographs, images, charts and information were selected from The Hospital for Sick Children teaching file, my personal collection or downloaded from the internet.

Dr. D. A. Jarvis

Learning Objectives

In this session participants will:

1. Review the common presentations of Sickle Cell Disease and emergency management

2. Learn some of the new emerging information on approaches to management

3. Be stimulated to review the care Sickle Cell patients receive in their practice settings

What is Sickle Cell Disease?1910 James Herrick described RBCs distorted by

polymerized, deoxygenated hemoglobin as “sickle shaped”

1922 Mason named condition “sickle cell anemia”

• a single missence mutation B globin gene (sixth codon)

• thiamine substituted for adenine results in valine residue replacing glutamic acid

Sickle Cell Genetics

Genotype Short NameBS/BS SCD:SSBS/BC SCD:SCBS/BO thalassemia SCD:SBO

BS/B+ thalassemia SCD:SB+

How do patients present?

• Newborn screening program

• Recurrent crises: vaso occlusive (pain) bacteremia/septicaemia

acute chest syndrome splenic/hepatic

sequestration stroke aplastic

Pathophysiology and Presentations

• recurrent ischemia due to vaso-occlusion• acute and chronic inflammation• haemolysis – associated vasculopathy

Clinical presentations:gallstones,retinopathy, priapism pulmonary hypertension, avascular bone necrosis

Individual clinical severity based on interaction of genetic/environmental factors and HbF levels

Vaso-Occlusive (Pain) Crisis:

• cause: ischemic tissue injury results from obstructed blood flow by sickled RBCs

• precipitants: infection, fever, acidosis, hypoxia, dehydration, sleep apnea, extremes

of heat and cold

• clinical: bone, back, abdomeninfants dactylitis (hand/foot syndrome)

Vaso-Occlusive (Pain) Crisis:

• Management:

accurate ongoing pain assessmentsmaintain hydration 1½ x maintenance 10 ml/kg bolus if morphine RX

adequate pain control± antipyretics and antihistaminesrule out other pathologies

• discharge planning: to ensure continued symptom relief and

appropriate follow up health care

Pain Scales

Pain Scales

RT 8 Year Old Boy• known “sickler” HbSS• presented with painful, swollen right upper arm,

unable to feed himself• pain on and off for one week treated at home with

acetaminophen and ibuprofen• family denies fever – concerned arm is swelling

and skin feels warm

On examination: pain 10/10 Temp 37.8°CelsiusEmergency staff called Child Protection Services when x-ray showed “new bone formation”

Was this appropriate? What is the diagnosis?

RT 8 Year Old Boy• family contacted Sickle Clinic Nurse for help

On further investigation: multifocal osteomyelitisSalmonella species

Admitted to hospital:intravenous antibiotics and surgical drainage

Further history: diarrhea one month earlier on visit to Caribbean, denied rectal bleeding or fever

There may be more than 1 pathological process present!SickKids Toronto suggests any axillary temperature > 37.5°C be

investigated

Bacteremia / Septicemia• sickle disorders result in susceptibility to

overwhelming infection with encapsulated organisms (pneumococcus / salmonella)

• prophylactic antibiotics save lives

• vaccinations essential

• prompt evaluation with ANY rise in temperature, appropriate cultures and broad spectrum antibiotics within 30 minutes of arrival in Emergency Department

• admission to hospital in most cases

JJ 6 Month Old Boy• newborn Sickle Screen positive, confirmed at four

months of age• family doctor referred baby to tertiary centre• before first visit developed a “cold” and temperature

of 38°C• family treated with acetaminophen• found lifeless in crib• post mortem diagnosis Pneumococcal Sepsis

Could this have been prevented?How are newly diagnosed sicklers managed in your Emergency?

Acute Chest Crisis:

causes: infectious – bacteria, virusesnon-infectious – pulmonary infarctionhypoventilation, fat embolus, pulmonary oedema

clinical: young children – fever + coughadults – severe pain, dysnoea, chillschest crises cause 25% SCD fatalitiesmay result in restrictive chronic lung disease

Chest Syndrome Management• oxygen saturation and/or oxygen Rx• blood culture + CBC diff + reticulocytes• chemistry + X match CXR + arterial gas• iv N/S 1-1 ½ maintenance, bolus only if in shock

DO NOT OVER HYDRATE• iv antibiotics• measure pain + morphine iv• review old records and consult expert may need an

exchange transfusion – must be in ICU

Acute Sequestration

Clinical:• sudden increase in spleen size, decrease in

haemoglobin and increase in reticulocytes• child may present with pallor, decreased activity or

irritability• after attack, spleen decreases in size

In Jamaican cohort: accounted for 24% deaths in first ten years of study

Sergeant

Acute Splenic SequestrationManagement:

• parental detection reduces mortality• after 2nd attack, further events occur at shorter

intervals, each associated with mortality• prophylactic splenectomy generally indicated after

2nd attack• no demonstrated disadvantages of splenectomy in

terms of post-splenectomy infections or deaths• beware of over-transfusion

Cerebrovascular Accidents and SCDClinical:

• 11% risk of stroke in HbSS patients by 20 years age 16% have “silent strokes”

• presentation may be subtle and transient:visual field defects / aphasiaacute changes in behaviourmotor dysfunction

First indication of stroke(s) may be school or behavioural difficulties

Hulbert et al Blood 2011 .... Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy....

Cerebrovascular Accidents and SCD

Management:

• CT study early may be normal

• MRI investigation of choice

• always rule out meningitis and other causes of altered mental status

• exchange transfusionNote: educational implications and need for multidisciplinary

follow up

AC 6 Year Old Girl

• A camp counsellor at Summer Camp notices 6 year old AC is watching activities today

• AC states she is “fine, just don’t feel like playing today”

How should the counsellor proceed?

What do you think is happening?

Sickle Cell Crisis Challenges• wide spectrum of presentations• stoic / calm patients versus distressed patients• low grade fever at home, “well” looking• patient with normal temperature in emergency• young patients reported to be “quieter” than usual

or “not usual selves”

Note: avoid underestimations of pain severity

early signs of sepsis, hypersplenism and aplastic crises may be subtle

multiple pathologies may be present

New emerging information

• can clinical severity be predicted?

• do all febrile “sicklers” need admission?

• how much fluid is enough?

• what is that heart murmur?

• how long do sicklers live?

• nitric oxide inhalation during pain crisis

Can clinical Severity be Predicted?Vanden Tweel Am J Hematol 2010; 85: 746-51Validated a pediatric severity index for sickle cell patients:

• Bone necrosis• Cerebral infarcts or vasculopathy• Hepatic / Splenic sequestration• Pneumococcal sepsis and / or meningitis• Priapism• Acute chest syndrome / Painful crises• Lab values: Hb ≤ 6.6 g/dl HbF ≤ 3.0%

LDH 700 U/I WBC ≥ 15.2

Do all febrile “sicklers” need admission?

Rogovik et al Am J Emerg Med 2010; 28: 511-4

• retrospective chart review 692 emergency visits during 2 year period – Toronto SickKids

• 77 % febrile Sickle Cell children admitted• 1.3% positive blood cultures no S. pneumoniae• most children had received 7 valent pneumoccal

conjugate vaccine

Ramakrishnan M et al Lancet Inf Dis 2010Increased risk of invasive bacterial infections in Africa....Suggest: CAUTION continue to treat and admit febrile sickle

cell patients until “low risk” criteria for discharge are validated

How much fluid is enough?Miller Pediatr Blood Cancer 2010; 54;265-8

1928 Dr. Hugh Josephs first noted that urine concentration defect common in sickle cell anaemia

• defect may be reversible with transfusions

• clinically nocturia, enuresis and tendency to dehydration seen

BABY HUG ongoing double blind, placebo controlled trial to evaluate efficacy of hydroxyurea in young sickle children to prevent end organ damage

Results: infants 7.5 to 17.9 months able to concentrate urine after fluid deprivation before enrolment

retesting of same children planned in 2 yearsNote: avoid over hydration of young infants

What is that murmur?• chronic anaemia• fluid overload• pulmonary hypertension: tricuspid regurgitation• pathology not related to sickle cell anaemia

Johnson 2010 BloodLeft ventricular hypertrophy and diastolic dysfunction... are related to asleep and waking oxygen saturation

Liem 2010 Am J HematologyReproducibility of tricuspid jet velocity measurements

Arslankoylu 2010 J Tropical PediatricsAssessment of cardiac functions... doppler myocardial performance index

Jamaican Cohort 6

Age 3 months Age 30 years

How long do Sicklers live?• depends on genetics, severity of disease, environment and access to medical care

ReferencesNitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis: a randomized trialGladwin MT, Kate GJ, Weiner D et alJAMA 2011; 305 (9): 893-902

Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)Wang WC et al, BABY HUG investigatorsThe Lancet 2011; 377: 1663-72

Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with Sickle Cell DiseaseHulbert ML, McKinstry RC, Lacey JL et alBlood 2011; 117: 772-79

The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Challenges of Study DesignThompson BW, Miller ST, Rogers ZR, Rees RC et alPediatr Blood Cancer 2010; 54: 250-55

ReferencesUrine Concentration Ability in Infants with Sickle Cell Disease: Baseline Data from the Phase III Trial of Hydroxyurea (BABY HUG)Miller ST, Wang WC, Iyer R et alPediatr Blood Cancer 2010; 54: 265-68

Outcome of children with sickle cell disease admitted to intensive care – a single institution experienceBartram JL, Thein SL, Gardner K et alBr J Haematol 2010; 150: 614-7

Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturationJohnson MC, Kirkham FJ, Redline S et alBlood 2010; 116(1): 16-21

Assessment of cardiac functions in Sickle Cell Anemia with doppler myocardial performance indexArslankoylu AE, Hallioglu O, Yilgor E, Duzovali OJ Trop Pediatr 2010; 56(3):195-7

ReferencesImproved survival of children and adolescents with sickle cell diseaseQuinn CT, Rogers RR, McCavit TL, Buchanan GRBlood 2010; 115: 3447-52

Development and validation of a pediatric severity index for sickle cell patientsvan Den Tweel XW, van der Lee JH, Heijboer H, Peters M, Fijnvandraat K

Am J Hematol 2010; 85: 746-51

The risks and benefits of long term use of hydroxyurea in sickle cell anaemia: A 17.5 year follow upSteinberg MH, McCarthy WF, Castro O et al; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-UpAm J Hematal 2010; 85: 403-8

Bacterial blood cultures in children with sickle cell diseaseRogovik AL, Friedman JN, Persaud J, Goldman RDAm J Emerg Med 2010; 28: 511-14

ReferencesIncreased risk of invasive bacterial infections in African people with sickle-cell disease: a systemic review and meta-analysisRamakrishnan M, Moisi JC, Klugman KP et alLancet Inf Dis 2010; 10:329-37

Pulmonary Complications of Sickle Cell DiseaseGladwin MT, Vichinsky ENEJM 2008; 359: 2254-65

Sickle Cell DiseaseDriscoll MCPediatrics in Review 2007; 28(7): 259-68

Sickle Cell DiseaseGraham R SergeantOxford Medical Publications